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Genome wide screen

Xiaolong Zhu, Juan Cai, Fan Zhou, Zulin Wu, Dan Li, Youbin Li, Zhiping Xie, Yiting Zhou, Yongheng Liang
Honokiol (HNK), an important medicinal component of Magnolia officinalis, is reported to possess pharmacological activities against a variety of diseases. However, the molecular mechanisms of HNK medicinal functions are not fully clear. To systematically study the mechanisms of HNK action, we screened a yeast mutant library based on the conserved nature of its genes among eukaryotes. We identified genes associated with increased resistance or sensitivity to HNK after mutation. After functional classification of these genes, we found that most HNK-resistant strains in the largest functional category were petites with mutations in mitochondrial genes, indicating that mitochondria were related to HNK resistance...
August 17, 2018: Traffic
Ruiqi Han, Li Li, Alejandro Piñeiro Ugalde, Arieh Tal, Zohar Manber, Eric Pinto Barbera, Veronica Della Chiara, Ran Elkon, Reuven Agami
BACKGROUND: Functional characterization of non-coding elements in the human genome is a major genomic challenge and the maturation of genome-editing technologies is revolutionizing our ability to achieve this task. Oncogene-induced senescence, a cellular state of irreversible proliferation arrest that is enforced following excessive oncogenic activity, is a major barrier against cancer transformation; therefore, bypassing oncogene-induced senescence is a critical step in tumorigenesis...
August 17, 2018: Genome Biology
Florence Koeppel, Alexandre Bobard, Céline Lefebvre, Marion Pedrero, Marc Deloger, Yannick Boursin, Catherine Richon, Romy Chen-Min-Tao, Guillaume Robert, Guillaume Meurice, Etienne Rouleau, Stefan Michiels, Christophe Massard, Jean-Yves Scoazec, Eric Solary, Jean-Charles Soria, Fabrice André, Ludovic Lacroix
Comprehensive genomic profiling using high-throughput sequencing brings a wealth of information, and its place in the clinical setting has been increasingly prominent. This review emphasizes the utility of whole-exome sequencing (WES) and transcriptome sequencing (RNAseq) in patient care and clinical research, based on published reports as well as our experience with the MOSCATO-01 (MOlecular Screening for CAncer Treatment Optimization) molecular triage trial at Gustave Roussy Cancer Center. In this trial, all contributive samples of patients with advanced solid tumors were analyzed prospectively with targeted gene sequencing (TGS) and comparative genomic hybridization...
July 2018: Cancer Journal
Mark Manzano, Ajinkya Patil, Alexander Waldrop, Sandeep S Dave, Amir Behdad, Eva Gottwein
Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus. Our understanding of PEL is poor and therefore treatment strategies are lacking. To address this need, we conducted genome-wide CRISPR/Cas9 knockout screens in eight PEL cell lines. Integration with data from unrelated cancers identifies 210 genes as PEL-specific oncogenic dependencies. Genetic requirements of PEL cell lines are largely independent of Epstein-Barr virus co-infection. Genes of the NF-κB pathway are individually non-essential...
August 15, 2018: Nature Communications
Federico Innocenti, Kouros Owzar, Chen Jiang, Amy S Etheridge, Raluca Gordân, Alexander B Sibley, Flora Mulkey, Donna Niedzwiecki, Dylan Glubb, Nicole Neel, Mark S Talamonti, David J Bentrem, Eric Seiser, Jen Jen Yeh, Katherine Van Loon, Howard McLeod, Mark J Ratain, Hedy L Kindler, Alan P Venook, Yusuke Nakamura, Michiaki Kubo, Gloria M Petersen, William R Bamlet, Robert R McWilliams
PURPOSE: Advanced pancreatic cancer is a highly refractory disease almost always associated with survival of little more than a year. New interventions based on novel targets are needed. We aim to identify new genetic determinants of overall survival (OS) in patients after treatment with gemcitabine using genome-wide screens of germline DNA. We aim also to support these findings with in vitro functional analysis. PATIENTS AND METHODS: Genome-wide screens of germline DNA in two independent cohorts of pancreatic cancer patients (from the Cancer and Leukemia Group B (CALGB) 80303 and the Mayo Clinic) were used to select new genes associated with OS...
2018: PloS One
Hirofumi Ichinose, Takuya Kitaoka
A wide variety of sesquiterpenoids have been isolated from basidiomycetes, and their bioactive properties have attracted significant attention in an effort to understand biosynthetic machineries. As both sesquiterpene synthases and cytochrome P450 monooxygenases play key roles in the diversification of sesquiterpenoids, it is important to widely and mutually understand their biochemical properties. In this study, we performed genome-wide annotation and functional characterization of sesquiterpene synthases from the brown-rot basidiomycete Postia placenta...
August 13, 2018: Microbial Biotechnology
Amit V Khera, Mark Chaffin, Krishna G Aragam, Mary E Haas, Carolina Roselli, Seung Hoan Choi, Pradeep Natarajan, Eric S Lander, Steven A Lubitz, Patrick T Ellinor, Sekar Kathiresan
A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation1 . Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature2-5 , it has not yet been possible to use polygenic predictors to identify individuals at risk comparable to monogenic mutations...
August 13, 2018: Nature Genetics
Yujiro Higuchi, Hitomi Matsufuji, Masanari Tanuma, Takatoshi Arakawa, Kazuki Mori, Chihaya Yamada, Risa Shofia, Emiko Matsunaga, Kosuke Tashiro, Shinya Fushinobu, Kaoru Takegawa
Pyruvyl modification of oligosaccharides is widely seen in both prokaryotes and eukaryotes. Although the biosynthetic mechanisms of pyruvylation have been investigated, enzymes that metabolize and degrade pyruvylated oligosaccharides are not well known. Here, we searched for a pyruvylated galactose (PvGal)-releasing enzyme by screening soil samples. We identified a Bacillus strain, as confirmed by the 16S ribosomal RNA gene analysis, that exhibited PvGal-ase activity toward p-nitrophenyl-β-D-pyruvylated galactopyranose (pNP-β-D-PvGal)...
August 13, 2018: Scientific Reports
Francesco Iorio, Fiona M Behan, Emanuel Gonçalves, Shriram G Bhosle, Elisabeth Chen, Rebecca Shepherd, Charlotte Beaver, Rizwan Ansari, Rachel Pooley, Piers Wilkinson, Sarah Harper, Adam P Butler, Euan A Stronach, Julio Saez-Rodriguez, Kosuke Yusa, Mathew J Garnett
BACKGROUND: Genome editing by CRISPR-Cas9 technology allows large-scale screening of gene essentiality in cancer. A confounding factor when interpreting CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes within copy number amplified regions of the genome. We have developed the computational tool CRISPRcleanR which is capable of identifying and correcting gene-independent responses to CRISPR-Cas9 targeting. CRISPRcleanR uses an unsupervised approach based on the segmentation of single-guide RNA fold change values across the genome, without making any assumption about the copy number status of the targeted genes...
August 13, 2018: BMC Genomics
Xun Chen, Jason Kost, Dawei Li
Many viruses are capable of integrating in the human genome, particularly viruses involved in tumorigenesis. Viral integrations can be considered genetic markers for discovering virus-caused cancers and inferring cancer cell development. Next-generation sequencing (NGS) technologies have been widely used to screen for viral integrations in cancer genomes, and a number of bioinformatics tools have been developed to detect viral integrations using NGS data. However, there has been no systematic comparison of the methods or software...
August 8, 2018: Briefings in Bioinformatics
Jasper A Diderich, Susan M Weening, Marcel van den Broek, Jack T Pronk, Jean-Marc G Daran
Saccharomyces pastorianus is an interspecies hybrid between S. cerevisiae and S. eubayanus . The identification of the parental species of S. pastorianus enabled the de novo reconstruction of hybrids that could potentially combine a wide array of phenotypic traits. Lager yeasts are characterized by their inability to decarboxylate ferulic acid present in wort, a phenotype also known as Pof - (phenolic off-flavor). However, all known S. eubayanus strains characterized so far produce clove-like aroma specific of 4-vinyl guaiacol, a decarboxylated form of ferulic acid...
2018: Frontiers in Microbiology
Ting Ding, Tingting Li, Jianrong Li
Pseudomonas fluorescens, a Gram-negative psychrotrophic bacteria, is the main microorganism causing spoilage of chilled raw milk and aquatic products. Quorum sensing (QS) widely exists in bacteria to monitor their population densities and regulate numerous physiological activities, such as the secretion of siderophores, swarming motility and biofilm formation. Thus, searching for quorum sensing inhibitors (QSIs) may be another promising way to control the deterioration of food caused by P. fluorescens. Here, we screened a traditional Chinese medicine (TCM) database to discover potential QSIs with lesser toxicity...
August 7, 2018: Bioorganic & Medicinal Chemistry
Dong-Myung Kim, Jeonghoon Heo, Dong Woo Lee, Mayumi Tsuji, Mihi Yang
To clarify reliable toxic mechanisms of bisphenol A (BPA), an endocrine disrupting chemical, we approached an alternative animal and whole genome analyses with the yeast knockout library (YKO) of Schizosaccharomyces pombe. As results, the 50% growth inhibition concentrations (GI50 ) of BPA was approximately 600 μM and the YKO-three step screening revealed the top 10 target candidate genes including dbp2, utp18, srs1, tif224, use1, qcr1, etc. The screening results were confirmed in human embryonic stem cell (hES)-derived hepatic cells and HepG2 human liver cancer cells...
August 11, 2018: Archives of Pharmacal Research
Paolo Devanna, Maartje van de Vorst, Rolph Pfundt, Christian Gilissen, Sonja C Vernes
Intellectual disability (ID) is a severe neurodevelopmental disorder with genetically heterogeneous causes. Large-scale sequencing has led to the identification of many gene-disrupting mutations; however, a substantial proportion of cases lack a molecular diagnosis. As such, there remains much to uncover for a complete understanding of the genetic underpinnings of ID. Genetic variants present in non-coding regions of the genome have been highlighted as potential contributors to neurodevelopmental disorders given their role in regulating gene expression...
August 10, 2018: Human Genetics
Keigo Morita, Yutaro Hama, Tamaki Izume, Norito Tamura, Toshihide Ueno, Yoshihiro Yamashita, Yuriko Sakamaki, Kaito Mimura, Hideaki Morishita, Wataru Shihoya, Osamu Nureki, Hiroyuki Mano, Noboru Mizushima
Macroautophagy is an intracellular degradation process that requires multiple autophagy-related ( ATG ) genes. In this study, we performed a genome-wide screen using the autophagic flux reporter GFP-LC3-RFP and identified TMEM41B as a novel ATG gene. TMEM41B is a multispanning membrane protein localized in the endoplasmic reticulum (ER). It has a conserved domain also found in vacuole membrane protein 1 (VMP1), another ER multispanning membrane protein essential for autophagy, yeast Tvp38, and the bacterial DedA family of putative half-transporters...
August 9, 2018: Journal of Cell Biology
G E Pollott
In animals, new autosomal recessive genetic diseases (ARGD) arise all the time due to the regular, random mutations that occur during meiosis. In order to reduce the effect of any damaging new variant, it is necessary to find its cause. To evaluate the best way of doing this, 34 papers which found the exact location of a new genetic disease in livestock were reviewed and found to require at least two stages. In the initial stage the commonly used χ 2 method, applied in a case-control association analysis with single nucleotide polymorphism (SNP)-chip data, was found to have limitations and was almost always used in conjunction with a second method to locate the target region on the genome containing the variant...
August 10, 2018: Animal: An International Journal of Animal Bioscience
Tianxi Cai, Yichi Zhang, Yuk-Lam Ho, Nicholas Link, Jiehuan Sun, Jie Huang, Tianrun A Cai, Scott Damrauer, Yuri Ahuja, Jacqueline Honerlaw, Jie Huang, Lauren Costa, Petra Schubert, Chuan Hong, David Gagnon, Yan V Sun, J Michael Gaziano, Peter Wilson, Kelly Cho, Philip Tsao, Christopher J O'Donnell, Katherine P Liao
Importance: Electronic health record (EHR) biobanks containing clinical and genomic data on large numbers of individuals have great potential to inform drug discovery. Individuals with interleukin 6 receptor (IL6R) single-nucleotide polymorphisms (SNPs) who are not receiving IL6R blocking therapy have biomarker profiles similar to those treated with IL6R blockers. This gene-drug pair provides an example to test whether associations of IL6R SNPs with a broad range of phenotypes can inform which diseases may benefit from treatment with IL6R blockade...
August 8, 2018: JAMA Cardiology
Mayadhar Barik, Minu Bajpai, Arun Malhotra, Jyotish C Samantaray, Sadananda Dwivedi, Sambhunath Das
Background: Craniosynostosis (CS) conditions are included with the premature fusion of one or more multiple cranial sutures. As the second leading and most common craniofacial anomaly and orofacial clefts globally. Syndromic and nonsyndromic CS (NSCS) occur as a part of a genetic syndrome unlike Apert, Crouzon, Pfeiffer, Muenke, and Saethre-Chotzen syndromes. Approximately, 90% of the cases of CS arises from NSCS group and it is now a great challenge for the researcher and neurosurgeon for Indian-origin children, a great burden worldwide...
April 2018: Journal of Pediatric Neurosciences
Neville E Sanjana
Genome-scale forward genetic screens elucidate the genetic basis of therapeutic resistance, tumor evolution, and metastasis in diverse human cancers.
August 8, 2018: Science Translational Medicine
Shushuai Yi, Jiangting Niu, Hualei Wang, Guoying Dong, Yanli Zhao, Hao Dong, Yanbing Guo, Kai Wang, Guixue Hu
BACKGROUND: Bocaviruses have been reported to cause respiratory tract infection and gastroenteritis in most animal species. In cats, different genotype bocaviruses have been identified in USA, Japan, Hong Kong and Portugal. However, the clear relationship between the clinical symptoms and FBoV infection is unknown, and the prevalence of FBoV and the distribution of FBoV genotypes in China are still unclear. RESULTS: In this study, 197 fecal samples from cats with diarrhea (n = 105) and normal cats (n = 92) were collected in different regions between January 2016 and November 2017 and investigated using PCR targeting different FBoV genotypes...
August 8, 2018: Virology Journal
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